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Biomedical subjects

J Si

Publications and source records attributed to J Si.

11 recordsLinked to original sources

Induction of acetylcholine receptor gene expression by ARIA requires activation of mitogen-activated protein kinase.

Transcription of genes encoding nicotinic acetylcholine receptor (AChR) subunits (alpha, beta, gamma or epsilon, and delta) is highest in nuclei localized to the synaptic region of the muscle, which contributes to maintain a high density of AChRs at the postjunctional membrane. ARIA (AChR inducing activity) is believed to be the trophic factor utilized by motor neurons to stimulate AChR synthesis in the subsynaptic area. To elucidate the signaling mechanism initiated by ARIA, we established stable C2C12 cell lines carrying the nuclear lacZ gene under the control of the mouse epsilon subunit promoter or chicken alpha subunit promoter. ARIA stimulated tyrosine phosphorylation of erbB proteins in these C2C12 cells within 15 s with a peak at 5 min. Immediately following tyrosine phosphorylation of erbB proteins, mitogen-activated protein (MAP) kinase was activated which occurred within 30 s and peaked at 8 min after ARIA stimulation. Concomitantly, expression of AChR genes was induced by ARIA. ARIA-induced AChR subunit transgene expression was observed only in differentiated myotubes and not in myoblasts, suggesting that downstream signaling component(s) are regulated in a manner dependent on the myogenic program. Inhibition of the MAP kinase activity by using a specific MAP kinase kinase inhibitor or by overexpressing dominant negative mutants of Raf or MAP kinase kinase attenuated or abolished the ARIA-induced activation of AChR alpha and epsilon subunit gene expression. These results indicate that regulation of AChR gene expression by ARIA in C2C12 cells requires activation of the MAP kinase signaling pathway.

Androstadienes

A computationally efficient method for solving the redundant problem in biomechanics.

Determining the optimal set of musculotendon forces with which to produce a forward dynamic simulation of movement typically involves a huge investment of time and computational resources. A new, computationally efficient method is proposed that simultaneously achieves the desired trajectory and the dynamically optimized set of muscle stresses, and hence forces, according to the maximal endurance criterion function of Crowninshield and Brand (1981). Muscle-induced accelerations of the system resulting from unit stress contractions of individual muscles are superposed via the new pseudoinverse method to yield the desired motion trajectory. The method is tested on a control problem involving a five degree-of-freedom (DOF), 30 muscle, upper extremity model, which incorporates a dual rigid-body forearm to represent pronation and supination more adequately. The pseudoinverse method delivered the desired motion to within 0.25 degrees for each DOF during a three-second simulation. It is anticipated that the methodology can be easily and accurately applied to other highly redundant optimal control problems in biomechanics.

Acceleration

Tyrosine phosphorylation and synapse formation at the neuromuscular junction.

Protein tyrosine phosphorylation is prevalent throughout the nervous system. It has been implicated to play an important role in the development and maintenance of neuronal functions. In the past few years significant advances have been made in our understanding of the molecular mechanisms of synapse formation and synaptic plasticity. Protein tyrosine phosphorylation appears to be important in the neuron-induced synthesis of the nicotinic acetylcholine receptor and aggregation of synaptic proteins at the neuromuscular junction during development. In addition, protein tyrosine phosphorylation may regulate the ion channel activity of the nicotinic acetylcholine receptor.

Animals

[Detection of p53 mutation using PCR-SSCP silver staining method].

A simple and sensitive technique to detect point mutation of the p53 gene using silver staining method for single-strand conformation polymorphism analysis of polymerase chain reaction (PCR-SSCP) is reported. In this study, the aberrations of the p53 gene (exon 6-8) in clinical specimens of primary cervical carcinoma were examined. Of 27 tumor tissues 2 samples showed mutations of p53 exon 7. Absence of abnormal bands in the p53 exon 6-8 in all ten normal cervical tissues. It appears that inactivation of p53 gene by point mutation is infrequent in clinical samples of human cervical carcinomas.

Base Sequence

[The reversing effect of HPV-16 E6E7 gene antisense plasmid on the HPV-16 positive human cervical carcinoma cells].

Antisense reconstruct, p16as E6E7Neo, harboring HPV-16E6E7 gene of which the expression is regulatable by dexamethasone was constructed. Calcium phosphate mediated transfection was employed to transduce this antisense reconstruct into HPV-16 positive CasKi cell line and HPV negative C-33A cell line (both derived from human cervical carcinoma) respectively. After dexamethasone was added into the culture medium to induce the expression of E6E7 antisense gene, the malignity of CasKi cells were reversed, while the growth characteristics and malignity of C-33A cells were unchanged. The results show that the reversing effect on CasKi cell is specific and mediated by inhibition of expression of E6E7 gene. It also demonstrated a more profound pathogenic role of HPV-16 E6E7 gene in the tumorogenesis of cervical carcinoma and provides a possibility for gene therapy of this tumor.

Animals

[Human papillomavirus, human cytomegalovirus and p53 gene in cervical carcinoma].

OBJECTIVE: To investigate the role of human papillomavirus (HPV) human cytomegalovirus (HCMV) infections and p53 gene mutations in the oncogenesis of cervical cancer and to clarify the association between p53 inactivation and the presence of HPV DNA. METHODS: We examined 38 primary cervical carcinomas and 21 normal cervical specimens for the presence of HPV and HCMV DNA sequences by multiple primers PCR and nest primers PCR. The structure of p53 gene (exons 6-8) was also analyzed by PCR-SSCP silver staining method. RESULTS: Mutations of p53 gene (exon 7) were detected in 2 of 38 tumors. One of the cases with p53 mutation was positive for HPV 16 and two positive for HCMV. HPV 16 and 18 infections were noted in 63.2% (24/38) of the tumors, the positive rate of HCMV was 84.2% (32/38). However, HPV 16,18 and HCMV infection occurred in 4.8% and 38.1% respectively in 21 normal cervical specimens. 21 of the 24 HPV 16,18 positive tumors were also HCMV positive, but none of the normal cervical tissues was infected with both HPV and HCMV. CONCLUSION: Detection of p53 mutations in cervical carcinoma is infrequent and apparently independent of HPV infection. Cervical carcinoma is strongly associated with HPV 16 and 18 infection. A synergistic interaction may occur between HPV and HCMV infections in the oncogenesis of cervical cancer.

Carcinoma, Squamous Cell

Prevalence of human papillomavirus DNA sequences in an area with very high incidence of cervical carcinoma.

To improve our understanding of the relationship and possible associations between human papillomavirus (HPV) infection and the development of cervical malignancies, the presence of multiple types of HPV DNA sequences in cervical carcinoma was determined in Chinese citizens living in two different geographical locations where the incidences of cervical carcinoma are either relatively low or extremely high. HPV DNA sequences were found in 88.5% (54 of 61) of Chinese cervical carcinoma patients living in Taiwan, where the prevalence of cervical carcinoma is 23.7 per 100,000 women. In contrast, in LueYang in Shanxi province, an area with a very high prevalence of cervical carcinoma (1,026 per 100,000 women), only 57.1% (28 of 49) of Chinese cervical carcinoma patients were found to be infected with genital HPV. This result seems to suggest that either the presence of HPV may have different implications in different populations or HPV infection may not be the only factor that determines the development of cervical carcinoma, at least in certain geographical areas. Recently acquired transient or chronic persistent HPV infection may have a different outcome with regard to cervical carcinogenesis. Alternatively, other factors, such as host determinants, may play a role in the development of cervical carcinoma.

Age Factors

[Study of histopathological and ultrastructural differences between condylomata acuminata and pseudocondyloma of vulvae].

Histopathological alterations of condylomata acuminata were characterized by hyperkeratosis, parakeratosis, acanthosis, elongation of the rete ridges, pseudoepitheliomatous hyperplasia, discrete or grouped koilocytes, proliferation and dilatation of dermal capillaries, lymphocytic and histocytic infiltration around dermal capillaries. Histopathological pattern of pseudocondyloma of vulvae were characterized by finger-shaped configuration, epithelium was similar to normal of mucous membrane without atypia. The lesion was composed of a rich vascular network surrounded by connective tissue and a mild lymphocytic infiltration. Ultrastructural alterations of condylomata acuminata were characterized by proliferation of basal cells, enlarged and swollen nuclei in all layers, 1-4 large nucleoli, 1-3 nuclear bodies, interchromatin granules and perichromatin granules in some proliferating nuclei, swollen mitochondria, dilated endoplasmic reticulum, and dissolved glycogen. Ultrastructural alterations of pseudocondyloma of vulvae were characterized by proliferation of mucomembranous epithelial cells, mild swollen nuclei, 1-2 nucleoli, no nuclear body interchromatin and perichromatin granule, the dilatation of interstitial capillaries, and abundant fibril bundles in the dermis. Thus, the histopathological and ultrastructural manifestations of condylomata acuminata and pseudocondyloma of vulvae were significantly different. It may be of help in differentiation between the two disease.

Adolescent

[Molecular and ultrastructural study on the relationship between human papillomavirus and female genital condyloma in China].

From the results of DNA hybridization, it has been shown that there is a close relationship between HPV 16 and human uterine cervical carcinoma in China, and also that the viral DNA is integrated into the cancer cell genome. Genital condyloma revealed a high positive hybridization rate with HPV 11 DNA, and the viral DNA presented as an episome apart from the cell genome. Under the electron microscope, the inter and perichromatin granules as well as nuclear bodies were observed in all biopsies with positive hybridization, but no HPV particle was found in cancer cells, besides these two kinds of chromatin granules. Human papillomavirus nucleocapsid particles were observed in the nuclei of some genital condyloma cells. Electron-dense matrix aggregates of different sizes were seen in the perinuclear cytoplasm and in the nuclei. This kind of structure may be related to the process of HPV maturity, but its nature remains to be studied.

Carcinoma, Squamous Cell